Chronic Δ9-Tetrahydrocannabinol Administration Reduces IgE+B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin.

Delta9-tetrahydrocannabinol (Δ9-THC) is the major psychoactive component of the cannabis plant. Δ9-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ9-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Here, we determine the chronic effect of Δ9-THC administration using 0.32 mg/kg or placebo (PBO), i.m., twice daily for 428 days on SIVmac251 infected male Chinese-derived rhesus macaques. Sixteen animals were divided into four study groups: Δ9-THC+SIV+, Δ9-THC+SIV-, PBO/SIV+ and PBO/SIV- (n = 4/group). One-month after daily Δ9-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIVmac251/CNS, which was isolated from the brain of a Chinese macaque with end-staged neuroAIDS. No significant differences in peak and steady state plasma viral loads were seen between Δ9-THC+SIV+ and PBO/SIV+ macaques. Regardless of Δ9-THC, all infected macaques displayed significant drop of CD4/CD8 T cell ratio, loss of CD4+ T cells and higher persistent levels of Ki67+CD8+ T cells compared with uninfected animals. Moreover, long-term Δ9-THC treatment reduced significantly the frequency of circulating IgE+B cells. Only one Δ9-THC+SIV+ macaque died of simian AIDS with paralyzed limbs compared with two deaths in the PBO/SIV+ group during the study period. These findings indicate that chronic Δ9-THC administration resulted in reduction of IgE+B cells, yet it unlikely enhanced pathogenic SIVmac251/CNS infection in male Rhesus macaques of Chinese origin.